DNA polymerase alpha subunit 2 (POLA2) (POLA2)

DNA polymerase alpha subunit 2 (POLA2), also known as the B subunit or p70, is a crucial regulatory component of the eukaryotic DNA polymerase alpha-primase complex. This complex is the only enzyme capable of initiating de novo DNA synthesis by creating RNA-DNA primers that serve as starting points for the more processive polymerases delta and epsilon. POLA2 acts as a structural link between the catalytic subunit (POLA1) and the primase subunits (PRIM1 and PRIM2), facilitating the recruitment of the complex to replication origins via interactions with the origin recognition complex (ORC) during the S phase of the cell cycle. Because it is essential for cellular proliferation, POLA2 is frequently overexpressed in many types of cancer, where its levels often correlate with poor prognosis and advanced disease stages. Therapeutic approaches targeting the Pol alpha complex, such as the use of aphidicolin and various nucleoside analogs, aim to induce replication arrest and apoptosis in rapidly dividing cells. However, the clinical utility of such agents is often restricted by systemic toxicity due to the target's fundamental role in genomic duplication across all healthy tissues.

Other names

DNA polymerase alpha subunit BDNA polymerase alpha 70 kDa subunitp70 subunitDNA polymerase alpha subunit B2DNA polymerase subunit alpha-2POLA2_HUMAN

Inhibition of the heterotetrameric DNA polymerase alpha-primase complex prevents the initiation of DNA synthesis by blocking the assembly and elongation of the RNA-DNA primer, thereby causing replication stress and cell cycle arrest.